Assem Magda, El-Araby Rady E, Al-Karmalawy Ahmed A, Nabil Reem, Kamal Mohamed A M, Belal Amany, Ghamry Heba I, Abourehab Mohammed A S, Ghoneim Mohammed M, Alshahrani Mohammad Y, El Leithy Asmaa A
Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Division of Oral Biology, Department of Periodontology, Tufts University School of Medicine, Boston, MA, United States.
Front Genet. 2023 Feb 13;14:1122864. doi: 10.3389/fgene.2023.1122864. eCollection 2023.
Acute myeloid leukemia (AML) was reported as the most common type of leukemia among adults. Galectins constitute a family of galactose-binding proteins reported to play a critical role in many malignancies including AML. Galectin-3 and -12 are members of the mammalian galectin family. To understand the contribution of galectin-3 and -12 promoter methylation to their expression, we performed bisulfite methylation-specific (MSP)-PCR and bisulfite genomic sequencing (BGS) of primary leukemic cells in patients with AML before receiving any therapy. Here, we show a significant loss of gene expression in association with promoter methylation. The lowest degree of expression was found in the methylated (M) group while the highest degree was in the unmethylated (U) group and the partially methylated (P) group expression lies in between. This was not the case with galectin-3 in our cohort unless the CpG sites analyzed were outside the frame of the studied fragment. We were also able to identify four CpG sites (CpG number 1, 5, 7& 8) in the promoter region of galectin-12; these sites must be unmethylated so that expression can be induced. As far as the authors know, these findings were not previously concluded in earlier studies.
急性髓系白血病(AML)据报道是成人中最常见的白血病类型。半乳糖凝集素构成了一个半乳糖结合蛋白家族,据报道在包括AML在内的许多恶性肿瘤中起关键作用。半乳糖凝集素-3和-12是哺乳动物半乳糖凝集素家族的成员。为了了解半乳糖凝集素-3和-12启动子甲基化对其表达的影响,我们对未接受任何治疗的AML患者的原发性白血病细胞进行了亚硫酸氢盐甲基化特异性(MSP)-PCR和亚硫酸氢盐基因组测序(BGS)。在此,我们显示基因表达的显著丧失与启动子甲基化相关。甲基化(M)组的表达程度最低,而未甲基化(U)组最高,部分甲基化(P)组的表达介于两者之间。在我们的队列中,半乳糖凝集素-3并非如此,除非分析的CpG位点在研究片段的框架之外。我们还能够在半乳糖凝集素-12的启动子区域鉴定出四个CpG位点(CpG编号1、5、7和8);这些位点必须未甲基化才能诱导表达。据作者所知,这些发现以前在早期研究中并未得出结论。